This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research is being done because we would like to learn about the patterns of expression and identify the possible inherited factors involved in the development of hand osteoarthritis (OA). Hand OA can be found in up to 85% of the population over 65 years of age. It is a chronic, degenerative disease of the joint cartilage that causes related changes in underlying bone, leading to joint tenderness and pain. More women than men are affected and hand OA occurs in all ethnic groups all over the world. The purpose of this study is to see if certain patterns of expression of hand OA occur in families and to identify genes that may be involved. We are studying families in which there is an individual who has been diagnosed with hand OA. We are asking brothers, sisters, parents, and/or adult children over age 45 as well as spouses/significant others, to consider participating. We propose to study 300 individuals with hand OA who have an available sibling/first degree family member with or without hand OA who is willing to participate in the study, for a total of 600 study subjects (300 sibling pairs) and 150 unaffected spouses as controls. This will be accomplished by recruiting 300 individuals with hand OA into our study and studying an average of 1.5 family members per subject. We will work to identify hand OA probands who have clinical and radiographic evidence of hand OA and have at least 1 living sibling/first degree relative who may or may not have hand OA using the following methods: investigators will approach patients during their outpatient clinical visit, referrals from other CSMC and non-CSMC physicians, or patients may self-refer in response to advertisements. A variety of recruitment materials will be used to inform patients of the study including: patient letters, doctor letters, brochures, flyers and email advertisements. Specific Aim 1: We will recruit 300 probands with clinical and radiographic hand osteoarthritis (OA) from an orthopedic hand surgical practice in order to perform a family genetic study. We will recruit 300 siblings regardless of whether not they have hand OA and 150 spouse controls. Clinical and radiographic data will be collected on all study subjects. Specific Aim 2: We will assess the familiality and heritability of hand osteoarthritis in this population. Specific Aim 3: We will identify genetic risk factors for clinical and radiographic phenotypes with the highest heritabilities using genetic linkage studies of candidate genes for Hand OA. Specific Aim 4: We will assess which specific molecular variation in a candidate gene that showed linkage in aim 3 is associated with the various features of hand osteoarthritis by genetic association studies.